mercaptopurine and Colorectal-Neoplasms

The association between thiopurines and colorectal neoplasia risk remains controversial in inflammatory bowel disease [IBD] patients. We performed a systematic review and meta-analysis examining this association.. A comprehensive search of the PubMed, EMBASE and Cochrane Library databases was performed to identify relevant literature. Random-effects models were applied to calculate the pooled odds ratio [OR] and relative risk [RR] with corresponding 95% confidence intervals [CIs] among case-control and cohort studies.. Eleven cohort and 16 case-control studies involving 95397 patients were included in this study. Overall, the use of thiopurines was associated with a reduced risk of colorectal neoplasia both in case-control [OR = 0.49, 95% CI: 0.34-0.70] and cohort studies [RR = 0.96, 95% CI: 0.94-0.98]. Moreover, a protective effect of thiopurines against advanced neoplasia [high-grade dysplasia and cancer] [OR = 0.51, 95% CI: 0.31-0.84 for case-control studies; RR = 0.96, 95% CI: 0.94-0.98 for cohort studies] and colorectal cancer [CRC] [OR = 0.56, 95% CI: 0.34-0.93 for case-control studies; RR = 0.96, 95% CI: 0.94-0.98 for cohort studies] was also observed. Furthermore, when the analysis was conducted on patients at a high risk for colorectal neoplasia, the chemopreventive effect was confirmed in patients with long disease duration [> 8 years] but not in those with extensive colitis or primary sclerosing cholangitis.. This study demonstrated that thiopurine use was associated with a reduced risk of colorectal neoplasia, advanced neoplasia and CRC in IBD patients, especially those with long disease duration [> 8 years].

Topics: Colorectal Neoplasms; Humans; Immunosuppressive Agents; Incidence; Inflammatory Bowel Diseases; Mercaptopurine; Protective Factors; Risk Factors

Crohn's disease (CD) is a chronic inflammatory disease that confers a higher risk of cancer than in the general population. New, large, population-based studies in the past decade show that patients with CD are at higher risk of colorectal, small bowel, melanoma, and cervical cancer. Patients who use thiopurines are at additional risk of development of lymphoma and nonmelanoma skin cancer. Preventive surveillance for cancers of the colorectum, skin, and uterine cervix is advised.

Topics: Colorectal Neoplasms; Crohn Disease; Early Detection of Cancer; Female; Humans; Immunosuppressive Agents; Intestinal Neoplasms; Intestine, Small; Lymphoma; Male; Melanoma; Mercaptopurine; Risk Factors; Skin Neoplasms; Uterine Cervical Neoplasms

Cancer may be a complication of inflammatory bowel disease (IBD) or its treatments. In older Crohn's disease and ulcerative colitis patients, the risk of malignancy is of particular concern. IBD diagnosis at an advanced age is associated with earlier development of colitis-associated colorectal cancer. Thiopurine use in older IBD patients is tied to an increased risk of non-Hodgkin's lymphoma, nonmelanoma skin cancer, and urinary tract cancers. Additionally, older age is accompanied by multimorbidity, an increased risk of malnutrition, and decreased life expectancy, factors that complicate the management of cancer in the elderly. The optimal approach to the increased risk of malignancy in older age IBD is appropriate cancer screening and medical treatment. This may include age-specific colorectal cancer screening and limiting UV radiation exposure. With a growing number of older IBD patients, further studies are necessary to delineate the risk of cancer in this population.

Topics: Age Factors; Aged; Colorectal Neoplasms; Early Detection of Cancer; Humans; Inflammatory Bowel Diseases; Lymphoma, Non-Hodgkin; Mercaptopurine; Skin Neoplasms; Urologic Neoplasms

Patients with inflammatory bowel disease (IBD) are at increased risk for developing colorectal neoplasia. Researchers have debated whether treatment of IBD with thiopurines reduces cancer risk. We performed a meta-analysis of thiopurine exposure and risk of colorectal dysplasia or cancer in patients with IBD.. We used MEDLINE, EMBASE, and Cochrane search engines and abstract books from international conferences to identify relevant literature. We included studies on thiopurine exposure and risk of colorectal neoplasia in patients with ulcerative colitis or Crohn's disease. We calculated pooled odds ratios (ORs) with 95% confidence intervals (CIs) and performed a meta-regression analysis of the effect of year of publication. Various sensitivity analyses were conducted.. Fifteen studies fulfilled the inclusion criteria. Overall, we did not observe a significant effect of thiopurines on risk for colorectal neoplasia (dysplasia and/or cancer) in patients with IBD (OR, 0.87; 95% CI, 0.71-1.06). The estimate did not change markedly in separate assessments of the 2 population-based studies (OR, 0.87; 95% CI, 0.59-1.29), the 13 clinic-based studies (OR, 0.87; 95% CI, 0.59-1.09), the 7 cohort studies (OR, 0.93; 95% CI, 0.67-1.28), or the 8 case-control studies (OR, 0.83; 95% CI, 0.65-1.08). Studies that used neoplasia (dysplasia or cancer) as outcomes tended to show that thiopurines had protective effects (OR for neoplasia, 0.72; 95% CI, 0.50-1.05); these effects were not observed in studies of colorectal cancer (OR, 0.90; 95% CI, 0.72-1.12) or in studies published in recent years (meta-regression; P = .16).. In a meta-analysis, we did not find a significant protective effect of treatment with thiopurines on the risk of colorectal neoplasia in patients with IBD.

Topics: Colorectal Neoplasms; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Mercaptopurine; Risk Assessment; Treatment Outcome

It has been proposed that effective disease control through abrogation of inflammation in IBD may also reduce CRC risk in these individual patients. This article summarizes the potential for medical therapy to reduce the risk of CRC via primary and secondary prevention, and offers practical ways in which a goal of mucosal improvement or healing may be incorporated into clinical practice.

Topics: Adenocarcinoma; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Cholagogues and Choleretics; Colonoscopy; Colorectal Neoplasms; Early Detection of Cancer; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Intestinal Mucosa; Mercaptopurine; Mesalamine; Tumor Necrosis Factor-alpha; Ursodeoxycholic Acid

Inflammatory bowel disease (IBD) is commonly treated with thiopurines such as azathioprine and mercaptopurine for the maintenance of remission. Studies examining chemopreventive of these medications on colorectal neoplasm in IBD patients have yielded conflicting results. We performed a meta-analysis to assess the role of thiopurines for this indication.. We performed a systematic search of PubMed, Web of Science, EMBASE and Cochrane to identify studies reporting colorectal neoplasm from IBD patients treated with thiopurines and conducted a meta-analysis of pooled relative risk (RR) using the random effects model.. Nine case-control and ten cohort studies fulfilled the inclusion criteria. The use of thiopurines was associated with a statistically significant decreased incidence of colorectal neoplasm (summary RR=0.71, 95% CI=0.54-0.94, p=0.017), even after adjustment for duration and extent of the disease, but there was high heterogeneity among studies (I(2)=68.0%, p<0.001). The RR of advanced neoplasm (high-grade dysplasia and cancer) was 0.72 (95%CI=0.50-1.03, p=0.070) and that of cancer was 0.70 (95% CI=0.46-1.09, p=0.111) for thiopurine-treated patients. Heterogeneity of the studies was affected by the sample size (

Topics: Azathioprine; Colorectal Neoplasms; Humans; Inflammatory Bowel Diseases; Mercaptopurine; Risk

It is anticipated that unraveling the human genome will have a direct impact on the management of specific diseases. Variations or mutations in genes involved in drug metabolism or disease pathophysiology in gastroenterology and hepatology are expected to have effect on response to therapy. The spectrum of diseases is vast. Thus, we focus this review on clinical pharmacogenetics of inflammatory bowel disease, Helicobacter pylori infections, gastroesophageal reflux disease, irritable bowel syndrome, liver transplantation, and colon cancer. Although only a few genotyping tests are used regularly in clinical practice, we anticipate that in the future there will be more routine use of many of the tests described in this review.

Topics: Antineoplastic Agents; Azathioprine; Biotransformation; Colorectal Neoplasms; Gastrointestinal Agents; Gastrointestinal Diseases; Genetic Predisposition to Disease; Genotype; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Liver Diseases; Liver Transplantation; Mercaptopurine; Patient Selection; Pharmacogenetics; Phenotype; Polymorphism, Genetic; Treatment Outcome

Ulcerative colitis and Crohn's disease both confer an increased risk of developing colorectal cancer. The use of 5-aminosalicylate as a remission-inducing agent has been long accepted. Its use as a potential chemoprophylactic agent has been proposed and is used by some practitioners. This review examines the most recent data on 5-aminosalicylate as a chemoprophylactic drug as well as ursodeoxycholic acid, folic acid, azathioprine, and 6-mercaptopurine.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Cholagogues and Choleretics; Colorectal Neoplasms; Folic Acid; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Mercaptopurine; Mesalamine; Treatment Outcome; Ursodeoxycholic Acid; Vitamin B Complex

Inflammatory bowel disease encompasses a group of diseases with poorly defined etiology that affect the digestive tract. These diseases are characterized by their chronic course and by periods of disease activity, of variable severity, that alternate with periods of clinical remission. In the last few years, inflammatory bowel disease has been the object of intense research, which has increased knowledge of the physiopathogenic mechanisms involved. This has enabled the development of a new generation of biotechnological drugs effective in patients previously considered to be refractory to medical treatment and has allowed the accumulated corticosteroid dose to be reduced and the indications for surgery and hospital admissions to be decreased, thus improving quality of life. In addition, some classical drugs have been demonstrated to be effective in recurrence prevention after surgery for Crohn's disease and in the prevention of dysplasia and colorectal cancer in inflammatory bowel disease.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Azathioprine; Certolizumab Pegol; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Colectomy; Colitis, Ulcerative; Colorectal Neoplasms; Controlled Clinical Trials as Topic; Crohn Disease; Cyclosporine; Gastrointestinal Agents; Humans; Immunoglobulin Fab Fragments; Immunosuppressive Agents; Inflammatory Bowel Diseases; Infliximab; Infusions, Intravenous; Mercaptopurine; Meta-Analysis as Topic; Polyethylene Glycols; Quality of Life; Rectal Fistula; Recurrence; Time Factors

Ulcerative colitis is a chronic inflammatory bowel disease. The disease is diagnosed on the basis of clinical parameters and endoscopic-histologic evaluation. 5-aminosalicylic acid (5-ASA, mesalamine) represents the first-line treatment of choice. For patients with distal and left-sided disease the use of rectal preparations is effective. Most patients respond to 5-ASA suppositories or to topic steroids such as budesonide suppositories or hydrocortisone foam. For patients with extended disease, oral medications are mandatory. In case of low- to moderate-grade inflammation, 5-ASA preparations should be implemented. In the case of severe disease treatment with steroids is required. Following induction of remission, prophylactic treatment with 5-ASA (1.5 g/d) should be maintained. For patients with frequent or severe relapses, immunosuppressive therapy with azathioprine or 6-mercaptopurine is indicated. In case of a fulminant course of disease, treatment with intravenous cyclosporine is required in patients who have not responded to high-dose intravenous steroids. When all conservative treatment options fail, proctocolectomy with construction of an ileoanal pouch should be performed. New therapeutic strategies such as infliximab and interferons are being evaluated in clinical trials. The long-term complications of ulcerative colitis include steroid-induced osteoporosis and anemia and should be treated adequately. Finally, the risk for development of colorectal cancer increases steadily with disease duration and dysplasia should be screened for by endoscopic surveillance programs.

Topics: Administration, Oral; Adrenal Cortex Hormones; Aminosalicylic Acids; Anemia; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Antiviral Agents; Azathioprine; Budesonide; Clinical Trials as Topic; Colectomy; Colitis, Ulcerative; Colonic Pouches; Colonoscopy; Colorectal Neoplasms; Cyclosporins; Gastrointestinal Agents; Humans; Hydrocortisone; Immunosuppressive Agents; Infliximab; Injections, Intravenous; Interferons; Mercaptopurine; Mesalamine; Osteoporosis; Placebos; Practice Guidelines as Topic; Recurrence; Remission Induction; Risk Factors; Suppositories; Time Factors

Topics: Colorectal Neoplasms; DNA; DNA Methylation; Humans; Inflammatory Bowel Diseases; Mercaptopurine; Proto-Oncogene Proteins c-vav

Patients with ulcerative colitis (UC) are at increased risk of developing colorectal cancer (CRC), but recent studies suggest a lower risk than previously reported. The aim was to evaluate the incidence of dysplasia, CRC and related risk factors in UC patients from a Spanish nationwide database.. All UC patients were identified and retrospectively reviewed. Clinical-epidemiological data and the finding of dysplasia and/or CRC were collected.. A total of 831 UC patients were included. Twenty-six cases of CRC in 26 patients and 29 cases of high-grade dysplasia (HGD) in 24 patients were found, accounting for 55 diagnoses of advanced neoplasia (AN = CRC and/or HGD) in 45 patients (33% of them within the first 8 years after UC diagnosis). The cumulative risk of AN was 2, 5.3 and 14.7% at 10, 20 and 30 years, respectively. Concomitant primary sclerosing cholangitis (odds ratio [OR] 10.90; 95% confidence interval [CI] 3.75-31.76, p < 0.001), extensive UC (OR 2.10, 95% CI 1.01-4.38, p = 0.048), UC diagnosis at an older age (OR 2.23, 95% CI 1.03-4.83, p = 0.043) and appendectomy prior to UC diagnosis (OR 2.66, 95% CI 1.06-6.71, p = 0.038) were independent risk factors for AN. Use of thiopurines (OR 0.21, 95% CI 0.06-0.74, p = 0.015) and being in a surveillance colonoscopy programme (OR 0.33; 95% CI 0.16-0.67; p = 0.002) were independent protective factors for AN.. The risk of AN among UC patients is lower than previously reported but steadily increases from the time of UC diagnosis. The widespread use of thiopurines may have influenced this reduced incidence of UC-related neoplasias.

Topics: Adult; Aged; Aged, 80 and over; Colitis, Ulcerative; Colorectal Neoplasms; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Incidence; Logistic Models; Male; Mercaptopurine; Middle Aged; Registries; Retrospective Studies; Risk Factors; Spain

Previous studies have suggested a chemopreventive effect of 5-aminosalicylic acid (5-ASA) therapy in patients with inflammatory bowel disease (IBD). This effect has not been reported in IBD patients using thiopurines. We investigated the association between thiopurine or 5-ASA use and the risk of advanced neoplasia (AN), including high-grade dysplasia and colorectal cancer, in a large cohort of patients with IBD in the Netherlands.. PALGA, the nationwide network and registry of histo- and cytopathology in The Netherlands was linked to an anonymised computerised database of a Dutch health insurance company to identify patients with IBD with or without AN. Pharmaceutical data, including type and duration of medication use, were collected between January 2001 and December 2009. Cox proportional hazard regression analysis was used to calculate risk of AN in patients with and without thiopurine or 5-ASA use.. A total of 2578 patients with IBD were included. Of these, 973 patients (38%) used 5-ASA, 314 (12%) thiopurines, 456 (18%) both 5-ASA and thiopurines and 835 (32%) none of these drugs. Twenty-eight patients (1%) developed AN during 16,289 person-years of follow-up. Of these, 11 patients (39%) had used 5-ASA, two (7%) thiopurines and one (4%) both drugs. Thiopurine use was associated with a significantly decreased risk of developing AN (adjusted HR 0.10, 95% CI 0.01 to 0.75). 5-ASA therapy also had a protective effect on developing AN, but this was not statistically significant (adjusted HR 0.56, 95% CI 0.22 to 1.40).. Thiopurine use protects IBD patients against the development of AN. The effect of 5-ASA appeared to be less pronounced.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Cohort Studies; Colorectal Neoplasms; Female; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Male; Mercaptopurine; Mesalamine; Middle Aged; Proportional Hazards Models; Risk

Topics: Azathioprine; Colorectal Neoplasms; Crohn Disease; Folic Acid; Humans; Inflammatory Bowel Diseases; Mercaptopurine; Mesalamine

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antimetabolites, Antineoplastic; Azathioprine; Colitis, Ulcerative; Colorectal Neoplasms; Humans; Mercaptopurine; Mesalamine

Evidence suggests that mesalamine-based anti-inflammatory medicines may prevent colorectal cancer (CRC) in ulcerative colitis (UC). If mesalamine exerts its chemopreventive effect by its anti-inflammatory activity, then other medications that reduce colitis activity also should possess chemopreventive properties. Our aim was to determine the effect of the immunomodulators 6-mercaptopurine (6MP) and azathioprine (AZA) in preventing the development of dysplasia or CRC in UC.. Patients with UC who underwent a surveillance colonoscopy in 1996-1997 were identified from a gastrointestinal pathology database. A proportional hazards analysis assessing 6MP/AZA use as a time-changing covariate was performed to evaluate the effect of 6MP/AZA on: (1) progression to any neoplasia (low-grade dysplasia, high-grade dysplasia, or CRC), and (2) progression to advanced neoplasia (high-grade dysplasia or CRC).. A total of 315 subjects met inclusion criteria and were followed for an average of 8 years from their first surveillance examination. There were no significant differences in rates of progression to advanced neoplasia or to any neoplasia between 6MP/AZA users and never-users by log-rank testing. The proportional hazards analysis resulted in hazard ratios of 1.06 (95% confidence interval, .59-1.93) and 1.30 (95% confidence interval, .45-3.75) when considering the effect of exposure to 6MP/AZA on progression to any or to advanced neoplasia, respectively. The results were unaffected by known potential confounders.. In UC patients with no initial history of dysplasia, 6MP/AZA use appears to have little or no effect on the rate of neoplastic transformation in the colon. Importantly, the use of 6MP/AZA did not increase malignant transformation in UC.

Topics: Adult; Azathioprine; Cell Transformation, Neoplastic; Colitis, Ulcerative; Colorectal Neoplasms; Disease Progression; Female; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Proportional Hazards Models

Topics: Administration, Oral; Administration, Rectal; Aminosalicylic Acids; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Azathioprine; Colitis, Ulcerative; Colorectal Neoplasms; Controlled Clinical Trials as Topic; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Mercaptopurine; Meta-Analysis as Topic; Patient Selection; Placebos; Proctitis; Remission Induction; Suppositories; Time Factors

Topics: Adolescent; Adult; Azathioprine; Bone Marrow; Child; Colorectal Neoplasms; Drug Hypersensitivity; Female; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Male; Mercaptopurine; Pancreatitis; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Randomized Controlled Trials as Topic